It has been suggested that at least some forms of alcoholism may be inherited. However, there are no objective biochemical or biological markers to ascertain this contention. Blass et al. have reported an abnormality in a thiamine pyrophosphate (TPP) requiring enzyme, transketolase (TK) in a post alcoholic thiamine deficiency disease, Wernicke-Korsakoff syndrome. This biochemical abnormality is genetic and has been suggested to be the predisposing factor for thiamine deficiency disease such as the Korsakoff syndrome. Since Km and affinity are inversely related, we measured the apparent Km for binding TPP to TK in skin fibroblasts of children at high risk for alcoholism and in fibroblasts from age and sex matched controls. Fibroblasts from Wernicke-Korsakoff syndrome patients served as positive controls. On the basis of apparent Km for TPP, the subjects in this study could be divided into three groups: Low Km, intermediate Km and high Km. The characteristic Km values in cells from a particular patient persisted in serial passages in tissue culture. It was found that 97% of children at low risk for alcoholism had a low Km, whereas, 75% of the intermediate Km and 95% of the high Km group were at high risk for this disease. One hundred percent of Wernicke-Korsakoff syndrome patients had very high Km (greater than 3 MuM) as previously reported by Blass et al. These data suggest that (a) there is polymorphism in the Km of TK for TPP and (b) high Km enzyme occurs more frequently in high risk children than in those with a low risk for alcoholism. Thus a putative genetic (biochemical) abnormality in adult Wernicke-Korsakoff psychosis is now being identified in children at high risk for alcoholism long before their exposure to ethanol. Additionally, animal models for human fetal alcohol syndrome and Wernicke-Korsakoff psychosis are now being developed. In this context, various neuropeptides including Beta-endorphine and enkephalins are now being investigated.